The most powerful and frequent airborne allergens are plant pollens and among these, grass elicits one of the most widely spread forms of plant allergens. Inhaled pollen and especially grass pollen, which contributes to allergic disorders in up to 25% of adults, represents a major cause of type I allergy response in to susceptible individuals. Amongst the allergic responses are allergic rhinitis, conjunctivitis, hives and seasonal asthma. The impact of type I allergy in industrialized countries has increased tremendously, especially in children, and is now becoming a major health problem.
Asthma is the most common chronic disease of the lung which affects between 5 and 15% of the population in the industrial world. It is an inflammatory disease characterized by recurrent attacks of airway obstruction, traditionally treatable by anti-inflammatory drugs, particularly steroids. Despite new treatments, the prevalence and morbidity of asthma have been oil the rise in the last two decades.
Asthma is characterized by two phases that occur after allergen exposure: early asthmatic reaction, EAR, involving early bronchoconstriction that occurs within minutes, and a late asthmatic reaction, LAR, involving subsequent inflammatory reaction of the airways, which occurs 4 to 8 hours later and characterized by thickening of the bronchial walls due to edema and inflammatory cell infiltration of lymphocytes, eosinophils and others. The asthmatic events commence with inhalation of a trigger allergen that is presented to the immune system. A specific IgE-allergen complex which forms, subsequently binds to a specific mast cell membrane receptor (FcεRI), thereby causing degranulation and release of bronchoconstrictors and pro-inflammatory mediators like histamine. As a result the airway smooth muscle contracts and the bronchial lumen becomes narrow, leading to an increase in airway resistance and shortness of breath. This EAR is self-limited and resolves spontaneously within 1 hour or by the use of adrenergic medication. However, after about 4 hours, due to the inflammatory process initiated by the IgE-allergen complex and the release of proinflammatory mediators, the bronchial walls become swollen. This late process (LAR) may be reversed or even preventable by the use of steroids.
Asthma, allergic rhinitis and atopic dermatitis are almost invariably accompanied by elevated levels of IgE. Genetic analyses of families have shown that bronchial hyperresponsiveness (BHR) and IgE levels are linked. Thus, in clinical practice, specific IgE-allergen (as demonstrated by skin testing or in vitro assays) is generally believed to be inextricably connected to the induction of allergic airway symptoms, and is used as a guide for environmental modification and immunotherapy. The interaction of IgE with antigen is known to lead to a variety of immunological sequelae. Cross-linking of IgE bound to mast cells by FcεRI triggers the release of preformed vasoactive mediators, synthesis of prostaglandins and leukotrienes, and the transcription of cytokines (proinflammatory mediators).
The grass allergen of group-I that belong to the β-expansin gene family shares a high degree of amino acid sequence similarity with allergens belonging to different groups, i.e., group II/III, regardless of their origin. Expansins comprise of two closely related families, α-expansins (not glycosylated) and β-expansins (glycosylated). Expansins are secreted cell wall proteins (˜26 kDa) and are known to be involved in the loosening of the plant cell wall during plant growth as well as in the fruit softening process. The presence of high levels of expansins in the pollen suggests their involvement in pollen germination and pollen penetration and growth through the pistil.
The expansins are composed of two distinct domains: a C-terminal cellulose binding domain (CBD) and an N-terminal domain that exhibits some sequence similarity with the family of 45 endo-glucanases. The CBD allows expansins to interact with the cellulose microfibrils of the plant cell walls and is known to be the minimal structure required for plant cell-wall expansion and disruption of cellulose fiber-to-fiber interactions. It is important to note that expansins also possess a cystein-proteinase activity that may further explain their abilities to contribute to the allergenic reaction.
Interestingly, the allergens belonging to families II/III are small proteins (˜10 kDa) that share ˜40% identity and ˜60% similarity with the amino acid sequence of the C-terminal (CBD) of the expansins, thus suggesting that the CBD part is the common antigen in these groups of proteins (allergen families I/II/III). A direct support for this observation comes from the presence of the IgE antigen epitopes specifically on the cellulose binding cleft of the CBD domain as known for the rye-grass (Lolium perenne), a major group I allergen Lol pI protein. In fact, two of the four predicted T-cell epitopes readily exposed on the surface of the CBD match with IgE-binding regions. Some of these predicted T-cell epitopes are localized in the flattened regions of the beta-sandwich exposing aromatic amino acids that are known to be involved in the recognition of the cellulose by the CBD part of this protein.
A further support for this model is given by the fact that the CBD domain also possesses the classical immunoglobulin-like folding structure known as the common IgE binding site. Furthermore, the Ig-like three-dimensional fold of the CBD of the Lol pI allergen strikingly resembles those of Der f2 and Der p2, the main group 2 of house dust mite allergens.
Tree pollens are major causes of pollinosis and among them olive pollen has high clinical relevance in many areas around the world. A small olive pollen protein, Ole e 10 (10 kDa) is recognized as a major inducer of type I allergy in humans. The ability of Ole e 10 to bind soluble polysaccharides has been known. Ole e 10 binds specifically to 1,3-β-glucans, in addition this protein shows sequence identity with the non-catalytic C-terminal domains of several plant 1,3-β-glucanases (27-53% identity, 44-69% similarity). The change in the secondary structure of Ole e 10 in the presence of laminarin is in agreement with the fact that CBMs appear to have pre-formed carbohydrate recognition sites that mirror the solution conformations of their target sugars. The biochemical activity of Ole e 10 is in agreement with the fact that callose (1,3-β-glucan) is one of the major component of the pollen tube wall. Thus, Ole e 10 could act as a carbohydrate-binding protein that interacts with 1,3-β-glucans during cell wall synthesis/degradation during pollen germination.
Attempts to prevent allergy by employing allergen inactivating agents for inactivating allergens in the environment by specific polysaccharides have been documented. US Patent Applications Nos. 2005/0197319 and 2005/0256082 disclose an allergen inactivating agent containing a polysaccharide having a cellulose ether or a starch ether backbone, which is said to be suitable for inactivation of house dust and other allergens in the environment by forming a non-specific adsorbing matrix.
US Patent Application NO. 2004/0082907 discloses an apparatus for dispensing a restricted amount of powdered materials particularly to the human nasal tract. This device was used by Josling et al (2003) and Emberlin et al (2006) for the intranasal delivery of natural cellulose in the treatment of allergy symptoms from hay fever, dust mites and animal dander. The authors hypothesized that the natural crystalline cellulose reacts with the nasal mucus to create a physical barrier to pollen dust.
Oxidized cellulose has been investigated as immobilizing fabric matrices for various agents such as drugs, enzymes and proteins (Raftery 1980). The release of phenylpropanolamine from an oxidized cellulose derivative of phenylpropanolamine was also investigated as having potential drug celivery properties (Zhu, 2004).
Additionally, microparticles of oxidized cellulose are used for homeostasis.